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June 2005, Volume 55, Issue 6

Student's Corner

Prescription Pattern of Benzodiazepines for Inpatients at a Tertiary Care University Hospital in Pakistan

Muhammad Rizwanullah Khawaja  ( Medical Student Class of 2006, The Aga Khan University, Karachi )
A. Majeed  ( Department of Psychiatry, The Aga Khan University, Karachi )
F. Malik  ( Department of Psychiatry, The Aga Khan University, Karachi )
K. A. Merchant  ( Department of Psychiatry, The Aga Khan University, Karachi )
M. Maqsood  ( Department of Psychiatry, The Aga Khan University, Karachi )
R. Malik  ( Department of Psychiatry, The Aga Khan University, Karachi )
S. Mazahir  ( Department of Psychiatry, The Aga Khan University, Karachi )
H. Naqvi  ( Department of Psychiatry, The Aga Khan University, Karachi )

Abstract

Objective: To determine the point prevalence of benzodiazepine prescriptions for inpatients at a tertiary care university hospital in Pakistan and to correlate it with prescription patterns of various specialties, indications and demographic variables of the patients.

Methods: This 24-hours point prevalence study was done at The Aga Khan University Hospital, Karachi. By convenient random sampling, 208 inpatients were interviewed. Patients' files were also studied to record the drugs administered. Data was entered into questionnaires and analyzed by SPSS 10.0.

Results: The point prevalence of the benzodiazepines was 21.2%. It was higher among males than females and among surgical than non-surgical patients. Midazolam was the most commonly used benzodiazepine, followed by Alprazolam and Lorazepam. Pre-anesthesia and psychiatric symptoms were the two most common indications. Oral route was used in 84% patients for drug administration and mean Valium equivalent dosage was 4.86mg/day. Mean length of prescription was 3 days. Longer duration of hospitalization was a significant predictor of the requirement of benzodiazepine prescription (p-value=0.020).

Conclusion: Prescription pattern of benzodiazepines at a tertiary care university hospital is similar to that reported in the developed countries through monitoring at various levels by physicians, clinical pharmacist and nursing staff. Data regarding the prescription pattern of benzodiazepines is scarce, and it needs to be expanded to formulate clear guidelines regarding their prescription (JPMA 55:259;2005).

Introduction

After discovery of first Benzodiazepine, Chlordiacepoxide, in 1957, a large number of similar compounds were quickly introduced in clinical practice, being the most successful drugs ever used.1 The most important differences among the variety of benzodiazepines are pharmacokinetic ones. Established indications are anxiety and sleep disorders, seizures, epilepsy, muscle-relaxation, induction of amnesia, pre-medication and sedation in emergency medicine. In recent years it has also been proven to be effective in the treatment of panic disorder and catatonia.2

Benzodiazepine compounds have become an accepted component in the lives of a large segment of our population.1 They are among the most prescribed and consumed medication groups in the world3 having a multifactorial action with social and psychological roots4 and often not fully supported by present state of scientific knowledge.1 Benzodiazepines are widely prescribed in the hospital setting in the absence of appropriate documentation.4

The long-time benzodiazepine use by a considerable part of the population and its adverse consequences such as somatic and cognitive side effects, interactions with other drugs and alcohol and its possible impairment of quality of life has provoked a critical discussion about the practice of prescribing benzodiazepine and the information provided by physicians.5 The existence of Benzodiazepine dependence was described in the early sixties with very high dose of chlordiazepoxide but it has become a real concern for the medical community since the late seventies with increasing number of reports of withdrawal symptoms.6 Patients taking these drugs for four months or more may develop symptoms of withdrawal, characterized by anxiety, dysphoria, malaise, depersonalization, and by perceptual changes such as hyperacusis and unsteadiness.7 According to several studies, Benzodiazepine overdose is the most common way of self-poisoning among the substance induced suicidal attempts accounting for 30%-40% in western literature8,9, but 80% in Pakistan due to availability of the drugs over the counter, a fact which can be generalized to most developing nations.10

According to a study by Gutierrez et al5, in-patients on benzodiazepines in department of internal medicine of a hospital were followed for one year. Fifty percent of the patients prescribed Benzodiazepine for the first time were taking the drug even after one year. Moreover, a local study done on in- and out-patients revealed that in 73.4% drug prescriptions, duration of treatment was not specified.11 Thus iatrogenic induction of benzodiazepine dependence is an issue, which needs immediate attention and intervention.12,13

A study was conducted at The Aga Khan University Hospital to establish the prescription pattern of Benzodiazepines among in-patients, to determine the common types used, most common indications and any possible associations of usage with the patient's demographic data and hospital settings.

Methods

This was a 24 hours cross-sectional study conducted at The Aga Khan University Hospital, Karachi. The data was collected from in-patients of Surgery, Medicine, Obstetrics & Gynecology, Paediatrics, Psychiatry, Day-Care and Private wards on principle of convenient random sampling. Seven fourth year medical students of The Aga Khan University collected the data on a single working day. The information was entered on a questionnaire specifically designed for the study. Three types of questions were asked in the questionnaire, patient socio-demographic data, hospital-settings and prescription of benzodiazepines during the stay in hospital. Socio-demographic data included patient's hospital record number, gender, age, marital status, profession, education, place of residence and monthly household income. Hospital setting information consisted of ward, physician in charge, admitting service, primary diagnosis and length of stay. Benzodiazepine prescription information included questions about the indication, type, dosage, frequency and route of administration and length of benzodiazepine administration in days including the day of data collection. The questions were answered by the patient themselves or their attendants. The information about the prescriptions was confirmed from the medical records and online pharmacy system to minimize the recall bias regarding the prescription of the drug. All members of the survey team sought informed consent from the patients or their attendants according to an approved protocol.

Data was entered in SPSS 10.0 (Statistical Package for Social Sciences 10.0) and same software was used for statistical analysis of the data to establish the prescription pattern of Benzodiazepines. Student's t-test and chi-square test were used to determine any association between the patient's data and need for the benzodiazepine prescription. A p-value of <0.05 was considered as the criteria of statistically significant association in all the cases.

Results

Of the 375 patients admitted on the study day, 208 were included. There were 53.70% females amd the mean age of the participants was 39.53 years. Of the total subjects, 64% were married, 27.1% single, 7.9% widowed and 1.0% divorced. There were 28.9% participants without any formal education. The mean and median monthly household income was Rs.26,200 (US$ 450) and Rs. 10,000 (US$ 175) respectively. Professionals and labourers were 10.8% each, businessmen and students were 8.7% each, 6.7% were retired and 12.3% could not be put in any category, with the reason being that the patient was too young to have a profession or be a student. Non-residents of Karachi comprised 19.5%. Mean length of admission at the hospital of the overall population was 6 days. These socio-demographic characters of the population are described in the first column of Table 1.

Out of 208 patients enrolled in the study, 44 (26 males, 18 females) were prescribed benzodiazepines on the study day. Thus the point prevalence of the benzodiazepine prescription at AKUH was 21.2%. The prevalence of benzodiazepine prescription among males and females was 27.37% and 16.36% respectively and that among surgical and non-surgical patients was 25.58% and 18.03%, respectively. Mean age of the patients prescribed benzodiazepines was 40.3 years. The mean length of hospitalization among them was 9 days. The characteristics of the patients prescribed benzodiazepines are also described in the second column of Table 1.

Table 1. Description and comparison of in-patients' characteristics who were prescribed Benzodiazepines and those who were not prescribed Benzodiazepines.
  Total (n=208) Prescribed (n=44) Not Prescribed (n=164) p-value
Gender %
     Male/Female 46.3/53.7 59.1/40.9 42.9/57.1 0.056
Age (years)
     Mean 39.5 40.3 39.3 0.799
Marital status %
     Married 64.0 57.1 65.8 0.296
     Un-married 36.0 42.9 34.2
Income %
     <Rs.10,000 53.8 66.7 51.0 0.424
     Rs. 10,001 - 50,000 34.2 23.8 36.5
     >Rs. 50,000 12.0

9.5 12.5
Education %
     Nil 28.9 25.0 29.9 0.953
     Primary 21.1 22.5 20.8
     Secondary 13.4 12.5 13.6
     Intermediate 10.8 10.0 11.0
     Graduates 17.5 22.5 16.2
     Postgraduates 8.2 7.5 8.4
Profession %
     Housewives 37.4 25.0 40.7 0.293
     Laborers 10.8 15.0 9.7
     Professionals 10.8 7.5 11.6
     Businessmen 8.7 10.0 8.4
     Students 8.7 17.5 6.5
     Retired 6.7 10.0 5.8
     Unemployed 3.1 5.0 2.5
     Landlords 1.5 2.5 1.3
     Others 12.3 7.5 13.5
Residence %
     Karachi 80.5 75.0 81.9 0.323
     Outside Karachi 19.5 25.0 18.1
LoA* (Days)
     Mean 6 9 5 0.020
Service %
     Surgical 41.3 50.0 39.0 0.189
     Non-surgical 58.7 50.0 61.0
* LoA: Length of admission

The most commonly prescribed benzodiazepine was Midazolam in 65.9% cases, followed by Alprazolam and Lorazepam in 11.4% each. Other benzodiazepine generics prescribed and proportion of different Benzodiazepines in terms of their pharmacokinetics are shown in Table 2. Mean Valium equivalent daily dosage of the drug among patients was 4.86mg/day. Mean length of benzodiazepine administration was about 3 days. In 84.1% cases the drug was administered orally while in the remaining 15.9% cases it was administered intravenously.

Table 2. Prescription pattern of benzodiazepines.
Type [%]
 
Midazolam 65.9
Alprazolam 11.4
Lorazepam 11.4
Temazepam 4.5
Bromazepam 2.3
Clonazepam 2.3
Lormetazepam 2.3
Duration of Action [%]
Short Acting 63.6
Intermediate Acting 31.8
Long Acting 4.6
Valium equivalent daily dosage [mg]
Mean 4.68
Median 3.35
Route of Administration[%]
Oral 84.1
Intravenous 15.9
Length of prescription [days]  
Mean [Range] 3 [1-10]
Median 1
Mode 1

Major indications for benzodiazepine prescription were pre-operative sedation and amnesia (40.9%) and in 9.1% of the cases the reason could not be established. These indications are described in Table 3.

Socio-demographic and hospital data was correlated with the need for prescription of benzodiazepine drugs. Association was sought between Age, Gender, Marital status, Profession, Monthly Household Income, Education, Residence, Surgical or non-surgical services and Length of admission at the hospital with Benzodiazepine prescription. Among these, length of admission at the hospital proved to be a significant predictor for benzodiazepine prescription (p-value 0.02). The summary of these finings is summarized briefly in last column of Table 1.

Discussion

The point-prevalence of Benzodiazepine prescription among inpatients was 21.2%. The prevalence among males in our study was higher than in females, which is contradictory to most studies carried out in community.12 However our result was in harmony with studies done among inpatients.13 The review of literature4,14,15 confirms that the prevalence of benzodiazepine prescription at AKUH is comparable to that anywhere in the world, in fact being lower than most of the reported prevalence. However, very little comparable data could be found from the local literature. It is noteworthy that most of the studies considered here are reporting the prevalence in developed countries, where the prescription of benzodiazepines is considered well regulated. Little data is available regarding developing countries.

              Table 3. Means of benzodiazepine prescription.
Indications for Prescribing Benzodiazepines (n=44)
Pre-operative sedation 40.9%

Psychiatric Symptoms 20.5%
Neurological diseases 9.1%
Malignancy 6.8%
Minor invasive procedures 6.8%
Other medical conditions 6.8%
Indications not established 9.1%
Admitting Services of Patients
Prescribed Benzodiazepines (n=44)
 
Internal medicine 22.7%
Orthopedic Surgery 18.2%
General Surgery 9.1%
Urology 6.8%
Other surgeries 9.1%
Oncology 6.8%
Pediatrics 11.4%
Psychiatry 11.4%
Obstetrics and gynecology 4.5%
Percentage of Patients Prescribed
Benzodiazepines in a ward (n=208)
 
C0 - Psychiatry ward 62.5%
D0 - Pediatrics ward 16.7%
B1 - Surgery ward 6.5%
C1 - General Medicine ward 40.0%
D1 - Day Care Surgery ward 80.0%
A2 and B2 - Obstetrics & Gynecology ward Nil
C2 - Medicine ward 10.0%
ICU - Intensive care unit 40.0%
P1, P2 and P3 - Private ward 21.4%

In our study, Midazolam, a short acting benzodiazepine was most commonly prescribed, the indications being preoperative sedation and anterograde amnesia. Alprazolam and Lorazepam, both intermediate acting, followed Midazolam and most frequent indication for these two were psychiatric symptoms like anxiety, insomnia, agitation and depression. There is remarkable discrepancy between the proportions of various types of benzodiazepines prescribed and their duration of action in different studies.4,16 Summers et al report majority of the benzodiazepines prescribed were long acting (55%) and intermediate-acting (20.7%), despite the fact that most indications (pre-anaesthetic and night-time sedation; total 71.6%) called for the shorter-acting drugs. This inconsistency seems to shadow the indications of individual benzodiazepines. Moreover, in our study as well as others4, indication for benzodiazepine usage could not be established in many cases. This clearly suggests that at most places regulation of benzodazepine prescription is either non-existent or not implemented in its true spirit.

In our study, benzodiazepines were prescribed more frequently by the surgeons than the physicians, psychiatrists or oncologists. However, this difference was not statistically significant. Zisselman et al also obtained similar results.4 The oncologists require palliative treatment so . Surendrakumar et al showed same proportion of benzodiazepine prescriptions from oncologists as in our study.17

No significant assocation has been documented between age, gender, marital status, economic conditions and the requirement for benzodiazepines.20,21 Neuropsychiatric disorders, ethnicity and length of hospitalization play an important role.4,16

In our study, only the length of admission to the hospital was a statistically significant predictor for benzodiazepine prescriptions. This can be attributed to the physical, emotional and financial constraints, during prolonged hospitalizations, causing anxiety.

There is a dire need to analyzed the prescription pattern of benzodiazepines to regulate their usage, more so in third world countries, where these drugs are available over the counter. More studies correlated with the indications of the individual types of benzodiazepines, would help to formulate guidelines for prescribing this group of drugs for various indications. Many studies have successfully reported the decrease in the benzodiazepine prescription by effective strategies18-22, which can be duplicated in most settings. Another concern is the dependence potential of the benzodiazepines, prescribed for the first time in hospital and continuing the prescription at discharge indefinitely, which has been confirmed in various studies.15-23 All these matters can only be solved in the presence of substantial and convincing data, which can steer the policies to regulate the prescription of benzodiazepines at all levels and their effective implementation.

Acknowledgements

The authors are grateful to Dr. Murad Moosa Khan, Chair and Professor, Department of Psychiatry, The Aga Khan University, Karachi for his guidance and support.

References

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